Breast Cancer Research and Treatment

, Volume 132, Issue 3, pp 793–805 | Cite as

Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer

  • Makiko Ono
  • Hitoshi TsudaEmail author
  • Chikako Shimizu
  • Sohei Yamamoto
  • Tatsuhiro Shibata
  • Harukaze Yamamoto
  • Taizo Hirata
  • Kan Yonemori
  • Masashi Ando
  • Kenji Tamura
  • Noriyuki Katsumata
  • Takayuki Kinoshita
  • Yuichi Takiguchi
  • Hideki Tanzawa
  • Yasuhiro Fujiwara
Clinical Trial


The purpose of the present study was to identify histological surrogate predictive markers of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC). Among 474 patients who received NAC and subsequent surgical therapy for stage II–III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens obtained before NAC were available. As controls, CNB specimens from 42 tumors of the hormone receptor-negative and HER2-positive (HR−/HER2+) subtype and 46 tumors of the hormone receptor-positive and HER2-negative (HR+/HER2−) subtype were also included. Histopathological examination including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis, and immunohistochemical studies for basal markers were performed, and the correlation of these data with pathological therapeutic effect was analyzed. The rates of pCR at the primary site were higher for TNBC (32%) and the HR−/HER2+ subtype (21%) than for the HR+/HER2− subtype (7%) (P = 0.006). Expression of basal markers and p53, histological grade 3, high TIL scores, and apoptosis were more frequent in TNBC and the HR−/HER2+ subtype than in the HR+/HER2− subtype (P = 0.002 for TIL and P < 0.001 for others). In TNBC, the pCR rates of tumors showing a high TIL score and of those showing a high apoptosis score were 37 and 47%, respectively, and significantly higher or tended to be higher than those of the tumors showing a low TIL score and of the tumors showing a low apoptosis score (16 and 27%, respectively, P = 0.05 and 0.10). In a total of 180 breast cancers, the pCR rates of the tumors showing a high TIL score (34%) and of those showing a high apoptosis score (35%) were significantly higher than those of the tumors showing a low TIL score (10%) and those of the tumors showing a low apoptosis score (19%) (P = 0.0001 and 0.04, respectively). Histological grade and basal marker expression were not correlated with pCR. Although the whole analysis was exploratory, the degree of TIL correlated with immune response appear to play a substantial role in the response to NAC in TNBC.


Triple-negative breast cancer Neoadjuvant chemotherapy Pathological complete response Tumor-infiltrating lymphocytes Tumor cell apoptosis 



We thank Mrs. Sachiko Miura and Mrs. Chizu Kina for excellent technical assistance. This study was supported in part by grants from the Ministry of Health, Labor, and Welfare, Japan, the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and the Princess Takamatsu Cancer Research Fund, Japan.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Makiko Ono
    • 1
    • 7
  • Hitoshi Tsuda
    • 2
    Email author
  • Chikako Shimizu
    • 1
  • Sohei Yamamoto
    • 3
  • Tatsuhiro Shibata
    • 4
  • Harukaze Yamamoto
    • 1
  • Taizo Hirata
    • 1
  • Kan Yonemori
    • 1
  • Masashi Ando
    • 1
  • Kenji Tamura
    • 1
  • Noriyuki Katsumata
    • 1
  • Takayuki Kinoshita
    • 5
  • Yuichi Takiguchi
    • 6
  • Hideki Tanzawa
    • 7
  • Yasuhiro Fujiwara
    • 1
  1. 1.Breast and Medical Oncology DivisionNational Cancer Center HospitalTokyoJapan
  2. 2.Clinical Laboratory Division, Department of PathologyNational Cancer Center HospitalTokyoJapan
  3. 3.Department of Basic PathologyNational Defense Medical CollegeTokorozawa, SaitamaJapan
  4. 4.Cancer Genomics Project, Pathology DivisionCenter for Medical Genomics, National Cancer, Center Research InstituteTokyoJapan
  5. 5.Breast Surgery DivisionNational Cancer Center HospitalTokyoJapan
  6. 6.Department of RespirologyGraduate School of Medicine, Chiba UniversityChibaJapan
  7. 7.Department of Clinical Molecular BiologyGraduate School of Medicine, Chiba UniversityChibaJapan

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